MAP kinase has been identified as one of a handful of cytoplasmic protein kinases that integrate and relay signals initiated by many different sorts of mitogenic stimuli in somatic cells. These stimuli include physiological mitogens like EGF, PDGF, and insulin, tumor promoters like phorbol esters, and several oncogene products. More recently MAP kinase has been implicated in a different sort of cell cycle regulation: it appears to act downstream from MPF at the G2-M transition of oocytes entering meiosis. It seems unlikely that MAP kinase is a key regulatory protein, and that an understanding of kinase will contribute in important ways to our understanding of the mitotic cell cycle in somatic cells, the meiotic cell cycle in oocytes, and oncogene-mediated malignant transformation. Here we propose to use a combination of biochemical and molecular biological approaches to identify, purify and clone the regulators of MAP kinase, and to define the biochemical and biological consequences of MAP kinase activation. We have chosen Xenopus oocytes and eggs for these studies; Xenopus eggs are not only an abundant source of MAP kinase, but they are also amenable to powerful methods for in vitro and in vivo depletion of endogenous MAP kinase and re-introduction of wild type and mutant MAP kinases. The key questions to be addressed are: 1.What sites in MAP kinase become phosphorylated, and how do these phosphorylations affect MAP kinase activity? 2. What tyrosine kinase is responsible for the tyrosine phosphorylation of MAP kinase? 3.What serine(threonine) kinase is responsible for the threonine phosphorylation of MAP kinase? 4.What biological processes are mediated by MAP kinase activation? 5.What proteins are phosphorylated by MAP kinase in vivo? Our central goal is to understand how MAP kinase contributes to the cell's decision to divide.